Phase I DNA vaccine trial begins in Nairobi
Bonnie Levings and Patricia Kahn
Keywords:  AIDS, Vaccines, Health, Biotechnology programmes/networks, Private industry, Public institute, Non-governmental organization/ Foundation, Intellectual property rights.
Correct citation: Levings, B. and Kahn, P. (2001), "Phase I DNA vaccine trial begins in Nairobi." Biotechnology and Development Monitor, No. 46, p. 8.

Over the past year, clinical trials of a two-component Human Immunodeficieny Virus (HIV) vaccine have begun in Oxford (UK) and Nairobi (Kenya). Both components are based on HIV subtype A, the predominant strain in East Africa. This vaccine is the first one based on an HIV strain common in Africa to have entered even this first phase of clinical testing, which evaluates a vaccine's safety profile and yields some preliminary data on its ability to induce immune responses.

Worldwide, there are some half-dozen different broad categories of vaccines undergoing early clinical testing, but only one (VaxGen 's HIV-envelope-based subunit vaccine) that has reached so-called Phase III trials, which evaluate whether a vaccine is effective in preventing disease.

The new vaccine was developed through a Vaccine Development Partnership (VDP) between University of Oxford (UK), the University of Nairobi (Kenya) and the International AIDS Vaccine Initiative (IAVI), with vaccine production taking place at Cobra Pharmaceuticals in the UK and at Impfstoffwerk Dessau-Tornau GmbH (IDT) in Germany. The University of Nairobi's new HIV Vaccine Evaluation Unit, housed in the Department of Medical Microbiology , will carry out clinical and laboratory work for the trial.

Prime-boost studies

Phase I testing of the first vaccine component - 'naked' DNA containing selected HIV genes and individual epitopes (the portions of proteins that evoke immune responses) - has been well underway in Oxford since August 2000, and Nairobi since February, 2001. Both trials are fully enrolled, and so far no adverse effects have been observed in the volunteers.

Trials of the second vaccine component, which contains the same HIV genes inserted into harmless viral vector (the Vaccinia virus strain Modified Virus Ankara , MVA), began in Oxford in March 2001 (now fully enrolled, with eight volunteers) and will start shortly in Nairobi.

Lastly, the two components will be tested in combination by vaccinating people first with HIV-DNA and then with the HIV-MVA vector. This strategy, known as a "prime-boost", has been found empirically to induce more potent immune responses in animals (rhesus macaques) than either component alone. The first prime-boost trial will begin in Oxford in August 2001.

Each of the components is designed to stimulate broad immune responses by T-lymphocytes, the arm of the immune system which recognizes and destroys host cells infected by viruses, against multiple HIV epitopes. (In contrast, the B-lymphocytes produce antibodies, which lead to the destruction of free virus in the blood.) The epitopes were identified in people infected with subtype A HIV strains circulating in Kenya, but many of them are also found among other HIV subtypes.

The scientific rationale for a T-cell based AIDS vaccine initially grew out of studies with sex-workers in Nairobi and elsewhere in Africa. A small minority of these women remain seronegative despite continual exposure to HIV, and were found to have significant levels of HIV-specific T-cells in their bloodstream. The study in Nairobi has been ongoing for over ten years and involves a collaboration among the groups of Andrew McMichael, Sarah Rowland-Jones and Rupert Kaul from Oxford, and J.J. Bwayo, Omu Anzala and Frank Plummer of Nairobi.

Intellectual property issues

The trial preparations included negotiations over intellectual property (IP) issues. In December 1999, the British Medical Research Council (MRC) had filed a patent on the HIV sequences used in the vaccine. It lists the Oxford researchers Andrew McMichael and Tomas Hanke as co-inventors, but no Kenyan investigator. Articles in the Kenyan press expressed concern over the issue of ownership, which affects Kenyan rights to the vaccine, and over issues of inventorship and how credit is given for the work.

In response, the three partners in the project (the MRC, the University of Nairobi and IAVI) issued a joint statement reiterating their commitment to developing an AIDS vaccine together and stating that the original patent was "filed in good faith to protect the candidate DNA vaccine from unauthorized third-party exploitation." But they also acknowledged that the formal basis of the partnership - two bilateral memoranda between MRC and Nairobi and between IAVI and MRC - was insufficient, since there were no written agreements among all three parties. That acknowledgment led to the formation of an Intellectual Property Task Force , which met in November 2000 and April 2001. The Task Force agreed that the partners should be equal owners of the vaccines and share any future revenues they generated. Under patent law, "ownership" is determined contractually and can be shared however the partners choose. In contrast, "inventorship" is strictly defined under patent law, and legal consultation led to the conclusion that inventors should not be changed in the patent.

The Vaccine Development Partnership is being formalized by a "Memorandum of Understanding" among the MRC, the University of Nairobi and IAVI. This agreement will provide a framework for future decisions on issues related to intellectual property. It will include a commitment to the principle that any licensed products which arise from the collaboration will be jointly owned by all three partners and that any revenues will be shared.

Bonnie Levings & Patricia Kahn*

*International AIDS Vaccine Initiative, 110 William Street, 27th Floor, New York, NY 10038-3901, USA.
Phone +1-212-847 1056, Fax +1-212-847 1112,
E-mail pkahn@iavi.org

Hanke, T. and McMichael, A.J. (2000), "Design and construction of an experimental HIV-1 vaccine for a year-2000 trial in Kenya." Nature Medicine, Vol. 6, pp. 951-955.

Levings, B. (2000), "Phase I DNA Vaccine Trial Begins in Nairobi." IAVI Report, Dec. 2000 - Jan. 2001, p. 3.

International AIDS Vaccine Initiative (IAVI), http://www.iavi.org

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